SUMO



SUMO is a small ubiquitin-like modifier which covalently attaches to cellular proteins to modify their function. SUMO is similar in structure but not in sequence to ubiquitin. In several organisms SUMO is called SMT3. The SUMO-conjugating enzyme is called UBC9. The sentrin specific protease (SEPN) cleaves the C-terminal peptide from SUMO which then can bind to E1. The images at the left and at the right correspond to one representative SUMO, i.e. the crystal structure of human SUMO-2 protein (1wm2).

SUMO
2k8h – SUMO – NMR – Trypanosoma brucei

1u4a – hSUMO-3 (mutant) – NMR – human

1a5r - hSUMO-1

1wm2, 1wm3, 2awt – hSUMO-2

SUMO+ubiquitin-like SUMO-conjugating enzyme
2vrr, 2uyz – mSUMO-1+UBC9

2pe6 - hSUMO-1+UBC9

SUMO+sentrin specific protease
2io0 – pre-hSUMO-2+SEPN2

2io1 - pre-hSUMO-3+SEPN2

2g4d - hSUMO-1+SEPN1

2iy1 - hSUMO-1+SEPN1 (mutant)

2iyd, 2ckh - hSUMO-2+SEPN1

1tgz - hSUMO-1+SEPN2

2io3 - pre-hSUMO-2+SEPN2 (mutant)+RAN GTPase-activating enzyme (mutant)

2iy0 - hSUMO-1+SEPN1 (mutant)+RAN GTPase-activating enzyme

SUMO+ubiquitin-conjugating enzyme
1z5s - hSUMO-1+E2+ RAN GTPase-activating enzyme

2bf8 - SUMO-1+E2 - bovine

SMT3
2k1f – SMT3 – Fruit fly

2eke – ySMT3+UBC9 – yeast

1euv – ySMT3+ULP1 protease

SUMO+other proteins
2asq – hSUMO-1+SUMO-binding motif in PIASX

3kyc, 3kyd – hSUMO+SUMO-activating enzyme

2rpq – hSUMO-3+activating transcription factor

1wyw - hSUMO-1+thymine DNA glycosylate

2d07 - hSUMO-3+thymine DNA glycosylate

2kqs - hSUMO-1+death domain-associated protein 6 fragment



Ubiquitin (Ub) and ubiquitin-like (Ubl) proteins attached to their target proteins and modulating the activities of those targets in various ways. Three types of evolutionarily conserved enzymes — E1 activating enzymes, E2 conjugating enzymes and E3 ligase enzymes — act sequentially through parallel yet distinct pathways to conjugate ubiquitin and Ubl proteins, such as SUMO and NEDD8, to their targets. The E1 enzyme uses the adenosine triphosphate (ATP) and magnesium to adenylate the C-terminal Ub/Ubl glycine, releasing pyrophosphate and resulting in adenosine monophosphate (AMP). A non-hydrolysable mimic of the acyl adenylate intermediate (AMSN) and mimic of the tetrahedral intermediate (AVSN) were constructed. In both these compounds the atom of phosphorus is replaced by sulfur (colored yellow ).

The structural alignment of the crystal structures for human SUMO E1 in complex with SUMO adenylate (AMSN) and tetrahedral intermediate (AVSN) analogues revealed opened conformation (SUMO1 in orange, SAE1 colored in blue , and other domains in darkviolet ) and closed conformation (SUMO1 in yellow , SAE1 colored in cyan , and other domains in magenta ), respectively. In the open conformation (3kyc) the distance between Cys domain (including Cys173) and mimic of the acyl adenylate intermediate AMSN is very long, while in the closed conformation (3kyd), the catalytic Cys173 is posioned near AVSN and SUMO1, so the overall structure revealed dramatic rearrangement. This large conformational change forms the <scene name='3kyc/Al/8'>E1~SUMO1-AVSN tetrahedral intermediate analogue. </StructureSection>

For better understanding of the difference between these two conformations you can see this morph (generated by using POLYVIEW-3D: http://polyview.cchmc.org/polyview3d.html; reload/refresh this page to restart this movie). Of note, in contrast to the previous figure, the same domains of these two structures (3kyc and 3kyd) are colored in the same colors (<font color='yellow'>SUMO1 in yellow, <font color='blue'>SAE1 colored in blue and <font color='darkviolet'>other domains in darkviolet ). The catalytic Cys173 is shown in the spacefill representation and colored green, AMSN (or AVSN) are shown in the spacefill representation and colored in CPK colors.